BACKGROUND AND AIMS: Failure in the eradication of H. pylori is a frequent occurrence. We assessed the effectiveness of a third-line, levofloxacin-containing, 10-day sequential treatment, in order to obtain eradication of H. pylori resistant patients in a clinical setting.METHODS: One-hundred and nineteen consecutive patients with proven two consecutive failures in curing H. pylori infection, containing either clarithromycin, bismuth or levofloxacin, were prospectively assessed. All patients received a 10-day sequential therapy with proton pump inhibitor (PPI) plus amoxicillin 1 g for the first 5 days, followed by PPI, levofloxacin 500 mg and tetracycline 500 mg for the remaining 5 days (all twice daily). One month after conclusion of therapy, endoscopy was performed in those patients for whom the examinations were clinically relevant. The remaining patients were checked by ¹³C-urea breath test.RESULTS: H. pylori eradication was obtained in 80 patients (per-protocol: 68.38%; on intention-to-treat: 67.23%). Twenty-nine patients (24.37%) experienced side-effects, but only two of them (1.68%) were withdrawn from the study.CONCLUSION: A 10-day sequential triple therapy containing amoxicillin, levofloxacin and tetracycline seems to be effective and safe in curing resistant H. pylori infection.